論文 - 詳細
| RRC ID | 84167 |
|---|---|
| 著者 | Frankel EB, Tiroumalechetty A, Su Z, Henry PS, Mueller BD, Jorgensen EM, Wu Y, Kurshan PT. |
| タイトル | Intracellular protein-lipid interactions drive presynaptic assembly prior to neurexin recruitment. |
| ジャーナル | Neuron |
| Abstract |
Neurexin cell-adhesion molecules regulate synapse development and function by recruiting synaptic components. Here, we uncover a mechanism for presynaptic assembly that precedes neurexin recruitment, mediated by interactions between cytosolic proteins and membrane phospholipids. Developmental imaging in C. elegans reveals that the intracellular active zone protein SYD-1 accumulates at nascent presynapses prior to its binding partner neurexin. Combining molecular dynamics simulations to model intrinsic interactions between SYD-1 and lipid bilayers with biochemical and in vivo validation of these predictions, we find that PIP2-interacting residues in the SYD-1 C2 domain are required for active zone assembly. Genetic perturbation of a PIP2-generating enzyme disrupts synaptic SYD-1 accumulation, while the PIP2-interacting domain of mammalian RIM1 can compensate for the SYD-1 C2 domain, suggesting functional homology between these proteins. Finally, we propose that the evolutionarily conserved γ-neurexin isoform represents a minimal neurexin sequence that stabilizes nascent presynaptic assemblies, potentially a core function of this isoform. |
| 巻・号 | 113(5) |
| ページ | 737-753.e6 |
| 公開日 | 2025-3-5 |
| DOI | 10.1016/j.neuron.2024.12.017 |
| PII | S0896-6273(24)00916-4 |
| PMID | 39814011 |
| PMC | PMC11886894 |
| MeSH | Animals Caenorhabditis elegans Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism Molecular Dynamics Simulation Presynaptic Terminals* / metabolism Synapses* / metabolism |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Bluesky |
| 各媒体での言及数の合計 | 13 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 線虫 | tm1233 |